title: Impact of response to prior chemotherapy in patients with advanced urothelial carcinoma receiving second-line therapy: implications for trial design.
abstract: BACKGROUND
  The prognostic impact of response to prior chemotherapy independent of performance status (PS), hemoglobin (Hb), liver metastasis (LM), and time from prior chemotherapy (TFPC) in the context of second-line therapy for advanced urothelial carcinoma (UC) is unknown.
  
  
  METHODS
  Six phase II trials evaluating second-line therapy (n = 504) were pooled. Patients who received prior therapy for metastatic disease were eligible for analysis if Hb, LM, PS, and TFPC were available. Response by Response Evaluation Criteria in Solid Tumors 1.0 to first-line therapy was recorded. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of registration using the Kaplan-Meier method.
  
  
  RESULTS
  A total of 275 patients were evaluable for analysis. Patients received gemcitabine-paclitaxel, cyclophosphamide-paclitaxel, pazopanib, docetaxel plus vandetanib/placebo, or vinflunine (2 trials). Those with prior response (n = 111) had a median OS of 8.0 months (95% confidence interval [CI], 6.8-9.4), compared with 5.9 months (95% CI, 5.0-6.6) for those without prior response (n = 164). Those with prior response had a median PFS of 3.0 months (95% CI, 2.6-4.0) compared with 2.6 months (95% CI, 2.0-2.8) in patients without response. Multivariable analysis did not reveal a significant independent impact of prior response on PFS and OS.
  
  
  CONCLUSIONS
  Best prior response in patients receiving prior chemotherapy for metastatic disease did not confer an independent prognostic impact with second-line therapy for advanced UC. Given that the setting of prior chemotherapy (metastatic or perioperative) has not appeared significant in a prior study, patients who received prior chemotherapy in perioperative or metastatic settings may be enrolled in the same second-line trial stratified for PS, Hb, LM, and TFPC.
authors.affiliation: McMaster University, Ontario, Canada.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Pond
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.forename: Ronan
authors.initials: R
authors.lastname: Fougeray
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.forename: Angela Q
authors.initials: AQ
authors.lastname: Qu
authors.forename: Guenter
authors.initials: G
authors.lastname: Niegisch
authors.forename: Peter
authors.initials: P
authors.lastname: Albers
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Lorenzo
authors.forename: Yacine
authors.initials: Y
authors.lastname: Salhi
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Galsky
authors.forename: Neeraj
authors.initials: N
authors.lastname: Agarwal
authors.forename: Andrea
authors.initials: A
authors.lastname: Necchi
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013534:Survival; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019459:Urothelium / Q000187:drug effects / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents
keywords: Advanced urothelial carcinoma; Prognostic factors; Response to prior chemotherapy; Second-line therapy